12-Month Maintenance Data Affirms Benefit of Adding L-Methylfolate With An Antidepressant for Relapse Prevention

BUENOS AIRES, Argentina--(BUSINESS WIRE)--In two randomized clinical trials, patients with major depressive disorder were given a medical food, Deplin^® (L-methylfolate), 7.5mg in one study and 15mg in the other, for the nutritional management of metabolic imbalances in depression along with an antidepressant. 54 percent of those who achieved remission (using the 17-item Hamilton Depression Rating Scale [HDRS-17] scores ≤7) in 30-60 days during the acute phase maintained remission in an optional 12-month open-label maintenance phase. No one relapsed in this phase (HDRS-17 > 15).

These findings were presented at a poster session at the World Psychiatric Congress today by George Papakostas, MD, Associate Professor of Psychiatry at Harvard Medical School and Director of Treatment-Resistant Depression Studies in the Department of Psychiatry at Massachusetts General Hospital in Boston, Massachusetts.

Twelve-month remission data are important as they suggest the long-term benefit of a therapy. Patients who are inadequate responders to antidepressant monotherapy are vulnerable to relapse/recurrence of major depressive disorder.

Patients were enrolled from one of two separate multi-center, double-blind, placebo- controlled trials to assess the efficacy and safety using the medical food, L-methylfolate, plus an antidepressant for MDD in partial or non-responders to selective serotonin reuptake inhibitors (SSRI).

All patients following a double-blind, placebo controlled trial of L-methylfolate used with an SSRI were offered participation in a long-term maintenance phase. Thirteen patients who achieved remission (HDRS-17 scores ≤7) in the acute phase opted to enter this 12 month open-label phase. Eleven participants elected to take 15mg L-methylfolate along with their SSRI. One participant chose 7.5mg L-methylfolate and 1 participant chose variable dosing.

Fifty-four percent of patients maintained remission and no one relapsed. There were no serious adverse events, no discontinuations due to adverse events, and no clinically significant new onset adverse events reported during the 12 month open-label phase for the remitted subjects¹.

These results suggest that Deplin^®, a medical food for the dietary management of the metabolic imbalances in depression taken with an SSRI may represent a safe, effective and well tolerated strategy for long-term treatment of patients with major depression disorder who inadequately respond to traditional treatment with SSRIs, a common class of drugs used to treat depression. Additionally, the results of the open-label maintenance phase offers evidence to suggest that the use of L-methylfolate assists in preventing relapse/recurrence of MDD while maintaining long-term remission in MDD. Future research is needed in order to further clarify the antidepressant role of L-methylfolate and potential biomarkers that may provide benefits toward the likelihood of remitting and maintaining remission with adjunctive L-methylfolate.²

About the Study

The initial randomized double blind phase of this study used a novel sequential parallel comparison design (or SPCD). There were two trials in the study. Results from the first of the two trials (n = 148) were used to inform the dosing of the second trial (n = 75). The first trial found 7.5 mg dosing of L-methylfolate and an SSRI was not significantly different in efficacy compared to placebo and SSRI. The second trial however found 15 mg dosing L-methylfolate and an SSRI was significantly superior on response rates and degree of improvement in depressive symptoms compared to placebo and SSRI.

Before beginning the study, all patients had to demonstrate inadequate response to one or two SSRIs. Antidepressants included in the randomized trial were therapeutic doses of fluoxetine, citalopram, paroxetine, escitalopram, and sertraline. Once the patients entered into the study, the SSRI doses remained constant. There was no significant difference in side effects reported with adjunctive L-methylfolate 15 mg. Rates of discontinuation due to adverse events were no different in the L-methylfolate 15 mg and SSRI group compared to the placebo and SSRI group.¹

Outcomes of Double Blind Phase

As previously reported at the American Psychiatric Association 2011 Annual Meeting, two primary outcome measures were used in the study: Rates of response (50 percent reduction) in the 17-question Hamilton Depression Rating Scale (HDRS-17) and degree of improvement (mean change) in HDRS-17. Both primary outcome measures used in the study achieved statistical significance.

The data showed that 32.3 percent of patients who were given 15 mg of Deplin^® combined with an SSRI responded after 30 days of treatment compared with 14.6 percent of patients who received SSRI with placebo (p=0.04).

A greater reduction in depressive symptoms using the mean change in HDRS-17 was found in the adjuvant Deplin^® arm compared with the adjuvant placebo arm--5.58 points versus 3.04 points (p=0.05).

Folate Deficiency & L-methylfolate

Scientists have long suspected an association between a deficiency in the bioactive form of folate and depression, and studies have been conducted to determine if the active form of folate can improve depression symptoms.³

L-methylfolate has been categorized as a Trimonoamine Modulator (TMM) because it is the only form of folate that can cross the blood-brain barrier to help regulate serotonin, norepinephrine and dopamine, the neurotransmitters associated with mood.³ In this randomized, placebo controlled study, Deplin^® (L-methylfolate) was chosen because of its ability to cross the blood brain barrier, its bioavailability and safety.

About Deplin^®

Deplin^® is a medical food dispensed by prescription for the clinical dietary management of the metabolic imbalances associated with depression. It should be used only under medical supervision.⁴

For more information visit http://www.deplin.com or see full prescribing information.

¹ Papakostas, George. American Psychiatric Association 2011 Annual Meeting. Honolulu, HI. 18 May 2011. Scientific and Clinical Report Presentation. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

² Papakostas, George. NCDEU 51st Annual Meeting. Honolulu, HI. 13 June 2011. Scientific and Clinical Report Presentation. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

³ Stahl SM. Novel Therapeutics for Depression: L-methylfolate as a Trimonoamine Modulator and Antidepressant Augmenting Agent. CNS Spectrums. 2007;12(10):739-44.

⁴ Deplin® Package Insert. Pamlab, L.L.C. 04/2011.